Heme oxygenase 1

Details

Name
Heme oxygenase 1
Synonyms
  • 1.14.14.18
  • HO
  • HO-1
  • HO1
Gene Name
HMOX1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021270|Heme oxygenase 1
MERPQPDSMPQDLSEALKEATKEVHTQAENAEFMRNFQKGQVTRDGFKLVMASLYHIYVA
LEEEIERNKESPVFAPVYFPEELHRKAALEQDLAFWYGPRWQEVIPYTPAMQRYVKRLHE
VGRTEPELLVAHAYTRYLGDLSGGQVLKKIAQKALDLPSSGEGLAFFTFPNIASATKFKQ
LYRSRMNSLEMTPAVRQRVIEEAKTAFLLNIQLFEELQELLTHDTKDQSPSRAPGLRQRA
SNKVQDSAPVETPRGKPPLNTRSQAPLLRWVLTLSFLVATVAVGLYAM
Number of residues
288
Molecular Weight
32818.345
Theoretical pI
8.68
GO Classification
Functions
enzyme binding / heme binding / heme oxygenase (decyclizing) activity / metal ion binding / phospholipase D activity / protein homodimerization activity / signal transducer activity
Processes
angiogenesis / cell death / cellular iron ion homeostasis / cellular response to arsenic-containing substance / cellular response to cadmium ion / cellular response to heat / cellular response to hypoxia / cellular response to nutrient / endothelial cell proliferation / erythrocyte homeostasis / excretion / heme catabolic process / heme oxidation / intracellular signal transduction / intrinsic apoptotic signaling pathway in response to DNA damage / iron ion homeostasis / low-density lipoprotein particle clearance / negative regulation of DNA binding / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of leukocyte migration / negative regulation of mast cell cytokine production / negative regulation of mast cell degranulation / negative regulation of muscle cell apoptotic process / negative regulation of neuron apoptotic process / negative regulation of sequence-specific DNA binding transcription factor activity / negative regulation of smooth muscle cell proliferation / porphyrin-containing compound metabolic process / positive regulation of angiogenesis / positive regulation of chemokine biosynthetic process / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of smooth muscle cell proliferation / positive regulation of vasodilation / protein homooligomerization / regulation of angiogenesis / regulation of blood pressure / regulation of sequence-specific DNA binding transcription factor activity / regulation of transcription from RNA polymerase II promoter in response to iron / regulation of transcription from RNA polymerase II promoter in response to oxidative stress / response to estrogen / response to hydrogen peroxide / response to nicotine / response to oxidative stress / small GTPase mediated signal transduction / small molecule metabolic process / smooth muscle hyperplasia / transmembrane transport / wound healing involved in inflammatory response
Components
caveola / cytosol / endoplasmic reticulum / endoplasmic reticulum membrane / extracellular space / membrane / nucleolus / nucleus / perinuclear region of cytoplasm
General Function
Signal transducer activity
Specific Function
Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Exhibits cytoprotective effects since excess of free heme sensitizes cells to undergo apoptosis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Microsome
Gene sequence
>lcl|BSEQ0021271|Heme oxygenase 1 (HMOX1)
ATGGAGCGTCCGCAACCCGACAGCATGCCCCAGGATTTGTCAGAGGCCCTGAAGGAGGCC
ACCAAGGAGGTGCACACCCAGGCAGAGAATGCTGAGTTCATGAGGAACTTTCAGAAGGGC
CAGGTGACCCGAGACGGCTTCAAGCTGGTGATGGCCTCCCTGTACCACATCTATGTGGCC
CTGGAGGAGGAGATTGAGCGCAACAAGGAGAGCCCAGTCTTCGCCCCTGTCTACTTCCCA
GAAGAGCTGCACCGCAAGGCTGCCCTGGAGCAGGACCTGGCCTTCTGGTACGGGCCCCGC
TGGCAGGAGGTCATCCCCTACACACCAGCCATGCAGCGCTATGTGAAGCGGCTCCACGAG
GTGGGGCGCACAGAGCCCGAGCTGCTGGTGGCCCACGCCTACACCCGCTACCTGGGTGAC
CTGTCTGGGGGCCAGGTGCTCAAAAAGATTGCCCAGAAAGCCCTGGACCTGCCCAGCTCT
GGCGAGGGCCTGGCCTTCTTCACCTTCCCCAACATTGCCAGTGCCACCAAGTTCAAGCAG
CTCTACCGCTCCCGCATGAACTCCCTGGAGATGACTCCCGCAGTCAGGCAGAGGGTGATA
GAAGAGGCCAAGACTGCGTTCCTGCTCAACATCCAGCTCTTTGAGGAGTTGCAGGAGCTG
CTGACCCATGACACCAAGGACCAGAGCCCCTCACGGGCACCAGGGCTTCGCCAGCGGGCC
AGCAACAAAGTGCAAGATTCTGCCCCCGTGGAGACTCCCAGAGGGAAGCCCCCACTCAAC
ACCCGCTCCCAGGCTCCGCTTCTCCGATGGGTCCTTACACTCAGCTTTCTGGTGGCGACA
GTTGCTGTAGGGCTTTATGCCATGTGA
Chromosome Location
22
Locus
22q12|22q13.1
External Identifiers
ResourceLink
UniProtKB IDP09601
UniProtKB Entry NameHMOX1_HUMAN
GenBank Protein ID35173
GenBank Gene IDX06985
GenAtlas IDHMOX1
HGNC IDHGNC:5013
General References
  1. Yoshida T, Biro P, Cohen T, Muller RM, Shibahara S: Human heme oxygenase cDNA and induction of its mRNA by hemin. Eur J Biochem. 1988 Feb 1;171(3):457-61. [PubMed:3345742]
  2. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. [PubMed:15461802]
  3. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed:10591208]
  4. Keyse SM, Tyrrell RM: Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A. 1989 Jan;86(1):99-103. [PubMed:2911585]
  5. Shibahara S, Sato M, Muller RM, Yoshida T: Structural organization of the human heme oxygenase gene and the function of its promoter. Eur J Biochem. 1989 Feb 15;179(3):557-63. [PubMed:2537723]
  6. Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest. 1999 Jan;103(1):129-35. [PubMed:9884342]
  7. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983]
  8. Gozzelino R, Jeney V, Soares MP: Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol. 2010;50:323-54. doi: 10.1146/annurev.pharmtox.010909.105600. [PubMed:20055707]
  9. Datta D, Banerjee P, Gasser M, Waaga-Gasser AM, Pal S: CXCR3-B can mediate growth-inhibitory signals in human renal cancer cells by down-regulating the expression of heme oxygenase-1. J Biol Chem. 2010 Nov 19;285(47):36842-8. doi: 10.1074/jbc.M110.170324. Epub 2010 Sep 20. [PubMed:20855888]
  10. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  12. Gottlieb Y, Truman M, Cohen LA, Leichtmann-Bardoogo Y, Meyron-Holtz EG: Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol. Haematologica. 2012 Oct;97(10):1489-93. doi: 10.3324/haematol.2012.063651. Epub 2012 Mar 14. [PubMed:22419571]
  13. Schuller DJ, Wilks A, Ortiz de Montellano PR, Poulos TL: Crystal structure of human heme oxygenase-1. Nat Struct Biol. 1999 Sep;6(9):860-7. [PubMed:10467099]
  14. Lad L, Wang J, Li H, Friedman J, Bhaskar B, Ortiz de Montellano PR, Poulos TL: Crystal structures of the ferric, ferrous, and ferrous-NO forms of the Asp140Ala mutant of human heme oxygenase-1: catalytic implications. J Mol Biol. 2003 Jul 11;330(3):527-38. [PubMed:12842469]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB01942Formic acidexperimental, investigationalunknownDetails
DB02073Biliverdine IX AlphaexperimentalunknownDetails
DB0246812-PhenylhemeexperimentalunknownDetails
DB039062-PhenylhemeexperimentalunknownDetails
DB04912StannsoporfininvestigationalunknownDetails
DB04803VerdohemeexperimentalunknownDetails
DB069141-({2-[2-(4-CHLOROPHENYL)ETHYL]-1,3-DIOXOLAN-2-YL}METHYL)-1H-IMIDAZOLEexperimentalunknownDetails
DB073421-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanoneexperimentalunknownDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknowninducerDetails
DB09221PolaprezincexperimentalunknowninducerDetails
DB14001alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknowninducerDetails
DB14002D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknowninducerDetails